The Imaging Core of the Cleveland Clinic Lerner Research Institute (LRI) and a group of twelve investigators (all NIH-funded) request funds to purchase a Leica TCS SP8 confocal microscope. It will replace a 15 year-old Leica SP2 that was purchased in 1999 with funds from NIH (1S10 RR13696-01). This scope, together with its 13 year-old counterpart in the Core, has been heavily used, with 343 registered users from 33 different departments over the last five years alone. Images from these two microscopes have been included in more than 450 publications, 67 of them in 2013. Leica stopped manufacturing the SP2 in 2006, and now many parts are no longer available. The increasingly frequent malfunctions are therefore harder to repair. This is also the case with an essential component of the instrument, the Coherent Enterprise UV laser. (Both Leica and Coherent will stop offering a service contract on this system within the next year.) There is not enough capacity on the existing confocal microscopes at the LRI to accommodate the needs of the current users of the SP2 system when breakdowns occur. Studies are delayed and the planning of experiments becomes uncertain. Confocal microscopy is an indispensable tool for the research programs of our major users. Thus, there is a pressing need to acquire a new confocal system to ensure that these investigators who currently use the existing SP2 system have uninterrupted access to a functional confocal microscope and avoid delays in data collection and publication. The new confocal will be placed in a well-established core facility where it will be a critical, broadly usd component of the research program at Cleveland Clinic and beyond. For the past twenty years the Imaging Core has provided leading-edge imaging equipment and expertise for the northern Ohio scientific community. It is a strong and successful Core in a significant research facility, maximizing the benefits it provides for a variety of health-related investigations. The instrument here requested is fundamental to such research, and essential to the projects presented herein.